Impact of hormone therapy on Medicare spending in the Women's Health Initiative randomized clinical trials.

BACKGROUND: Randomized trials can compare economic as well as clinical outcomes, but economic data are difficult to collect. Linking clinical trial data with Medicare claims could provide novel information on health care utilization and cost. METHODS: We linked data from Medicare claims of women ≥65 years old who had Medicare fee-for-service coverage with their clinical data from the Women's Health Initiative trials of conjugated equine estrogens plus medroxyprogesterone acetate (CEE+MPA) versus placebo and of CEE-alone versus placebo. The primary outcome was total Medicare spending during the intervention phase of the trial, and the secondary outcomes were spending on diseases hypothesized a priori to be sensitive to the effects of hormone therapy. RESULTS: In the CEE+MPA trial, 4,557 participants ≥65 years old were included. Women randomly assigned to CEE+MPA had 4% higher mean Medicare spending overall ($45,690 vs $43,920, P = .08) but 0.5% lower spending for hormone-sensitive diseases ($3,526 vs $3,547, P = .07), with 73% higher spending for coronary heart disease (P = .045) and 122% higher spending for pulmonary embolism (P = .026). In the CEE-alone trial, 3,107 participants were included. Total spending among women randomly assigned to CEE was 3.3% higher ($75,411 vs $72,997, P = .16), and 1.7% higher spending for hormone-sensitive diseases ($5,213 vs $5,127, P = .57), but with 39% lower spending for hip fracture (p<0.03). CONCLUSIONS: Menopausal hormone therapy increased spending for some diseases, but decreased spending for others. These offsetting effects led to modest (3%-4%), nonsignificant increases in overall spending among women aged 65 years and older.

Venous thromboembolism and cardiovascular disease complications in menopausal women using transdermal versus oral estrogen therapy.

OBJECTIVE: To evaluate the risk of venous thromboembolism (VTE) and cardiovascular disease (CVD) complications, and assess healthcare costs in menopausal women using an estradiol transdermal system versus oral estrogen therapy (ET). METHODS: Health insurance claims from 60 self-insured US companies from 1999 to 2011 were analyzed. Women at least 50 years of age, newly initiated on transdermal or oral ET, were included. Cohorts were matched 1:1 based on exact factors and propensity score-matching methods. The incidence rate ratios (IRRs) of CVD complications, as well as VTE and other CVD events separately, were assessed through conditional Poisson models. Cohorts were also compared for healthcare costs using linear regression models to assess per-patient per-month cost differences. Confidence intervals (CIs) and P values were determined using a nonparametric method for cost outcomes. RESULTS: From each cohort, 2,551 users were matched to form the study population. A total of 274 transdermal ET users developed CVD complications compared with 316 women in the oral ET cohort (adjusted IRR 0.81; 95% CI, 0.67-0.99). Transdermal ET users also incurred lower adjusted all-cause and VTE/CVD-related healthcare costs relative to oral ET users (all-cause per-patient per-month cost difference [95% CI] = $41 [-34; 137], P = 0.342). CONCLUSIONS: This large matched-cohort study based on real-world data suggests that women receiving transdermal ET have significantly lower incidences of CVD events compared with those receiving oral ET, and that they also incur lower healthcare costs.

The economic impact of symptomatic menopause among low-socioeconomic women in the United States.

BACKGROUND: Menopausal symptoms have a significant negative impact on patient's quality of life and increase healthcare costs among women. METHODS: This retrospective analysis used data from a U.S. national database (01 January 2008-31 December 2010). Patients with a diagnosis of menopause symptoms or a prescription claim for hormone therapy were matched to control patients. Healthcare resource utilization and costs during the 6-month follow-up period were compared. Generalized linear models were used to adjust for differences in baseline and demographic characteristics between the cohorts. RESULTS: A total of 71,076 patients were included in each cohort. Patients with menopausal symptoms were more likely to have depression and anxiety and incurred significantly higher follow-up healthcare costs ($7237 vs $6739, p < 0.001) and healthcare utilization during the 6-month follow-up period. CONCLUSION: Patients diagnosed with menopausal symptoms or treated with hormone therapy incurred significantly higher healthcare costs than those without menopausal symptoms or treatment.

Patterns of resource utilization and cost for postmenopausal women with hormone-receptor-positive, human epidermal growth factor receptor-2-negative advanced breast cancer in Europe.

BACKGROUND: Healthcare resource utilization in breast cancer varies by disease characteristics and treatment choices. However, lack of clarity in guidelines can result in varied interpretation and heterogeneous treatment management and costs. In Europe, the extent of this variability is unclear. Therefore, evaluation of chemotherapy use and costs versus hormone therapy across Europe is needed. METHODS: This retrospective chart review (N = 355) examined primarily direct costs for chemotherapy versus hormone therapy in postmenopausal women with hormone-receptor-positive (HR+), human epidermal growth factor receptor-2-negative (HER2-) advanced breast cancer across 5 European countries (France, Germany, The Netherlands, Belgium, and Sweden). RESULTS: Total direct costs across the first 3 treatment lines were approximately €10,000 to €14,000 lower for an additional line of hormone therapy-based treatment versus switching to chemotherapy-based treatment. Direct cost difference between chemotherapy-based and hormone therapy-based regimens was approximately €1900 to €2500 per month. Chemotherapy-based regimens were associated with increased resource utilization (managing side effects; concomitant targeted therapy use; and increased frequencies of hospitalizations, provider visits, and monitoring tests). The proportion of patients taking sick leave doubled after switching from hormone therapy to chemotherapy. CONCLUSIONS: These results suggest chemotherapy is associated with increased direct costs and potentially with increased indirect costs (lower productivity of working patients) versus hormone therapy in HR+, HER2- advanced breast cancer.

A multicentric study regarding the use of hormone therapy during female mid-age (REDLINC VI).

BACKGROUND: Menopausal hormone therapy (HT) has shown benefits for women; however, associated drawbacks (i.e. risks, costs, fears) have currently determined its low use. OBJECTIVE: To determine the prevalence of current HT use among mid-aged women and describe the characteristics of those who have never used, have abandoned or are currently using HT. In addition, reasons for not using HT were analyzed. METHOD: This was a cross-sectional study that analyzed a total of 6731 otherwise healthy women (45-59 years old) of 15 cities in 11 Latin American countries. Participants were requested to fill out the Menopause Rating Scale (MRS) and a questionnaire containing sociodemographic data and items regarding the menopause and HT use. RESULTS: The prevalence of current HT use was 12.5%. Oral HT (43.7%) was the most frequently used type of HT, followed by transdermal types (17.7%). The main factors related to the current use of HT included: positive perceptions regarding HT (odds ratio (OR) 11.53, 95% confidence interval (CI) 9.41-14.13), being postmenopausal (OR 3.47, 95% CI 2.75-4.36) and having a better socioeconomic level. A total of 48.8% of surveyed women had used HT in the past, but abandoned it due to symptom improvement or being unconcerned; fear of cancer or any other secondary effects were also reported but in less than 10%. Among women who had never used HT, 28% reported the lack of medical prescription as the main reason, followed by the absence of symptoms (27.8%). Among those reporting lack of prescription as the main reason for not using HT, 30.6% currently had severe menopausal symptoms (total MRS score > 16); 19.5% of women were using alternative 'natural' therapies, with 35.1% of them displaying severe menopausal symptoms as compared to a 22.5% observed among current HT users. CONCLUSION: The use of HT has not regained the rates observed a decade ago. Positive perceptions regarding HT were related to a higher use. Lack of medical prescription was the main reason for not using HT among non-users, many of whom were currently displaying severe menopausal symptoms.

Hormone replacement therapy and the association with coronary heart disease and overall mortality: clinical application of the timing hypothesis.

Conclusions from randomized controlled trial (RCT) data over the past 10 years has spanned from presumed harm to consistency with observational data that hormone replacement therapy (HRT) decreases the risk for coronary heart disease (CHD) as well as overall mortality in women who are recently postmenopausal. Multiple clinical studies including randomized trials and observational studies converge with animal experimentation to show a consistency that HRT decreases CHD risk and overall mortality in primary prevention when HRT is started at the time of or soon after menopause. The totality of data supports the "timing" hypothesis that posits that HRT effects are dependent on when HRT is started in relation to age and/or time-since-menopause. The totality of data shows that HRT decreases CHD and overall morality when started in women who are less than 60 years old and/or less than 10 years postmenopausal, providing a "window-of-opportunity". Further evidence shows that women who start HRT when in their 50s and continued for 5-30 years that there is an increase of 1.5 quality-adjusted life-years (QALYs). Additionally, HRT is highly cost-effective at $2438 per QALY gained. The totality of data converges to show a consistency between randomized trials and observational studies that when started in women at or near menopause and continued long-term, HRT decreases CHD and overall mortality compared with women who do not use HRT. This article is part of a Special Issue entitled 'Menopause'.

Education, income, and incident heart failure in post-menopausal women: the Women's Health Initiative Hormone Therapy Trials.

OBJECTIVES: The purpose of this study is to estimate the effect of education and income on incident heart failure (HF) hospitalization among post-menopausal women. BACKGROUND: Investigations of socioeconomic status have focused on outcomes after HF diagnosis, not associations with incident HF. We used data from the Women's Health Initiative Hormone Trials to examine the association between socioeconomic status levels and incident HF hospitalization. METHODS: We included 26,160 healthy, post-menopausal women. Education and income were self-reported. Analysis of variance, chi-square tests, and proportional hazards models were used for statistical analysis, with adjustment for demographics, comorbid conditions, behavioral factors, and hormone and dietary modification assignments. RESULTS: Women with household incomes <$20,000 a year had higher HF hospitalization incidence (57.3/10,000 person-years) than women with household incomes >$50,000 a year (16.7/10,000 person-years; p < 0.01). Women with less than a high school education had higher HF hospitalization incidence (51.2/10,000 person-years) than college graduates and above (25.5/10,000 person-years; p < 0.01). In multivariable analyses, women with the lowest income levels had 56% higher risk (hazard ratio: 1.56, 95% confidence interval: 1.19 to 2.04) than the highest income women; women with the least amount of education had 21% higher risk for incident HF hospitalization (hazard ratio: 1.21, 95% confidence interval: 0.90 to 1.62) than the most educated women. CONCLUSIONS: Lower income is associated with an increased incidence of HF hospitalization among healthy, post-menopausal women, whereas multivariable adjustment attenuated the association of education with incident HF.

Burden of illness of hypertension among women using menopausal hormone therapy: a US perspective.

OBJECTIVE: To estimate the burden of illness (BOI) of hypertension in a cohort of women receiving menopausal hormone therapy (HT). METHODS: Patients with at least one prescription for menopausal HT were selected from the PharMetrics database during the period July 1, 2003, to June 30, 2005. Hormone therapy patients were divided into those with and without hypertension. The nonhypertensive cohort was propensity score-matched to the hypertensive cohort, controlling for patient demographics, overall comorbidities, and type of HT use. The BOI of hypertension in the menopausal HT cohort was defined as the difference in average annual total healthcare expenditures per person between the cohorts. RESULTS: The prevalence of menopausal HT use was 9.75% among potentially eligible patients in this commercially insured sample. Hypertension was the most common comorbidity in the menopausal HT cohort, with a prevalence of 34%. Hormone therapy patients with hypertension (n = 106,729) had significantly higher average annual healthcare expenditures compared to matched HT patients without hypertension ($8908 vs. $5960 per person per year; difference of $2948; p < 0.001). CONCLUSIONS: Hypertension is the most common comorbidity among menopausal HT users in the United States. The annual BOI of hypertension is both substantial and significant when compared to matched patients without hypertension, averaging $2948 per patient per year.

Cost-effectiveness of hormone therapy in the United States.

OBJECTIVE: To estimate the cost-effectiveness of 5 years of treatment with hormone therapy (HT) compared with no treatment for women with menopausal symptoms in the United States. METHODS: A Markov cohort simulation model was used with tunnel techniques to assess the cost-effectiveness of HT in women aged 50 years, based on a societal perspective. Clinical data, where possible, used results taken from the Women Health Initiative (WHI). The model had a lifetime horizon with cycle lengths of 1 year and contained the following disease states: hip fracture, vertebral fracture, wrist fracture, breast cancer, colorectal cancer, coronary heart disease, stroke, and venous thromboembolic events. An intervention was modelled by its impact on the disease risks during and after stopping treatment. The model required data on clinical effects, risks, mortality rates, quality of life weights, and costs. The main outcome of the model was cost per quality-adjusted life-year (QALY) gained on HT compared with no treatment. RESULTS: The results indicated that it was cost-effective to treat women with menopausal symptoms with HT in the United States. The severity of menopausal symptoms was the single most important determinant of cost-effectiveness, but HT remained cost-effective even where symptoms were mild or effects on symptom relief were small. CONCLUSIONS: Treatment of women with menopausal symptoms with HT is cost-effective.

Undertreatment of menopausal symptoms and novel options for comprehensive management.

OBJECTIVE: There is currently a gap in treatment options for menopausal symptoms and a need for comprehensive therapies that are safe and effective for postmenopausal women. This review discusses challenges in the management of menopausal symptoms and the effect of the Women's Health Initiative (WHI) study findings on current treatment patterns. It also examines present and future therapies. RESEARCH DESIGN AND METHODS: A literature search was conducted using Medline, the Cochrane Database, and the National Heart Lung and Blood Institute WHI website with the following search terms: primary care, menopause, vasomotor symptoms, hormone therapy, osteoporosis, and vaginal atrophy. Searches were limited to articles published between 1995 and 2009. RESULTS: Comprehensive therapies that target several aspects of menopause, such as vasomotor symptoms and chronic disease prevention, are currently hormone based. These hormone-based approaches are considered more effective than currently available nonhormonal therapies for the relief of menopausal symptoms. However, hormone therapy is not recommended for women at high risk for venous thromboembolic events, cardiovascular disease, and/or breast cancer. A need exists for novel therapies that mitigate menopausal symptoms, provide protection from osteoporosis, and encourage patient compliance without promoting cancer, heart disease, or stroke. Emerging modalities and strategies, such as the tissue selective estrogen complex (TSEC), Org 50081, MF101, and desvenlafaxine, may provide improved options for postmenopausal women. CONCLUSIONS: Several new menopausal therapies that may help to address the ongoing unmet need for safe and effective therapies for postmenopausal women are currently in development. In particular, the TSEC, which provides the benefits of both a selective estrogen receptor modulator and conjugated estrogens with an improved tolerability profile, may offer advantages over currently available treatment options. Limitations of this review include the narrow search criteria and limited search period.

Socioeconomic factors in menopausal women's use of hormone replacement therapy.

This study examines if education, income, and medical insurance coverage are primary factors in determining whether menopausal women use hormone replacement therapy (HRT). To accomplish this purpose, the author conducted a survey of 62 women between 30 and 60 years of age. These women completed a self-administered questionnaire that provided both quantitative and qualitative information. The results suggest that these socioeconomic factors increase the likelihood that menopausal women will receive treatment with HRT. Implications for clinical practice are discussed.

Cost-effectiveness of hormone replacement therapy for menopausal symptoms in the UK.

OBJECTIVE: To estimate the cost-effectiveness of five-year treatment of hormone replacement therapy (HRT) compared with no treatment for women with menopausal symptoms in the UK. METHOD: A Markov cohort simulation model with tunnel techniques was used to assess the cost-effectiveness of HRT in women aged 50 years. For the clinical effects of HRT we used, where possible, results taken from the Women's Health Initiative (WHI). The model had a life-time horizon with cycle lengths of one year and contained the following disease states: hip fracture, vertebral fracture, wrist fracture, breast cancer, colorectal cancer, coronary heart disease, stroke and venous thromboembolic events. An intervention was modelled by its impact on the disease risks during and after stopping treatment. The model was populated with UK-specific data on risks, mortality rates, quality-of-life weights and costs. The main outcome of the model was cost per quality-adjusted life year (QALY) gained of HRT compared with no treatment. RESULTS: The results indicated that it was cost-effective to treat women with menopausal symptoms with HRT in the UK. The severity of menopausal symptoms was the single most important determinant of cost-effectiveness, but HRT remained cost-effective even where symptoms were mild or effects on symptom relief were small. CONCLUSIONS: Treatment of women with menopausal symptoms with HRT is cost-effective.

The cost-effectiveness of hormone therapy in younger and older postmenopausal women.

PURPOSE: To evaluate the health and economic outcomes of hormone therapy in younger and older postmenopausal women. METHODS: We developed a cost-effectiveness model to evaluate outcomes associated with hormone therapy in younger and older postmenopausal women, using data sources from published literature through March 2008. The target population was 50-year-old and 65-year-old women given hormone therapy or no therapy, and then followed over their lifetime. Primary outcomes measured were quality-adjusted life-years (QALYs) and incremental cost per QALY gained. RESULTS: For the base-case analysis, hormone therapy for 15 years in the younger cohort resulted in a gain of 1.49 QALYs with an incremental cost of $2438 per QALY gained, compared with no therapy. The results for younger women were robust to all sensitivity analyses, and treatment remained highly cost-effective (<$10,000 per QALY gained) within the range of individual assumptions used. Treatment durations of 5 years and 30 years also were highly cost-effective. In the older cohort, treatment for 15 years resulted in a net gain of 0.11 QALYs with a cost of $27,953 per QALY gained. However, a loss of QALYs was seen in the first 9 years. The results for older women were sensitive to many of the assumptions used. CONCLUSIONS: Hormone therapy for 5 to 30 years in younger postmenopausal women increases quality-adjusted life-years and is cost-effective. Hormone therapy started in later years results in a loss of quality-adjusted life for several years before a net gain can be realized.

Cost effectiveness of hormone therapy in women at high risks of fracture in Sweden, the US and the UK--results based on the Women's Health Initiative randomised controlled trial.

OBJECTIVE: The purpose of the study was to assess the cost effectiveness of hormone therapy (HT) for postmenopausal women without menopausal symptoms at an increased risk of fracture in Sweden, the UK and the US. METHODS: Using a state-transition model, the cost effectiveness of 50 year old women was assessed based on a societal perspective and the medical evidence found in the Women Health Initiative (WHI) trials. The model had a lifetime horizon divided into cycle lengths of 1 year and comprised the following disease states: hip fracture, vertebral fracture, wrist fracture, breast cancer, colorectal cancer, coronary heart disease, stroke and venous thromboembolic events. An intervention was modelled by its impact on the disease risks during and after the cessation of treatment. The model required data on clinical effects, risks, mortality rates, quality of life weights and costs valid for Sweden, the UK and the US. The main outcome of the model was cost per QALY gained of HT compared to no treatment. RESULTS: The results indicated that HT compared to no treatment was cost-effective for most sub-groups of hysterectomised women, whereas for women with an intact uterus without a previous fracture, HT was commonly dominated by no treatment. Fracture risks were the single most important determinant of the cost effectiveness results. CONCLUSIONS: HT is cost-effective in women with a hysterectomy irrespective of prior fracture status. In women with an intact uterus, opposed HT was cost-effective in those with a prior vertebral fracture, but cost-ineffective in women without a prior vertebral fracture. Even though HT is found cost-effective for a selection of osteoporotic women, it is unlikely to be considered for first-line therapy for osteoporosis because bisphosphonates have shown a similar reduction in fracture risks but without an increased risk of adverse events.